Preclinical models of advanced melanoma have shown that chronic indomethacin therapy combined with interleukin 2 (IL-2) can eradicate experimental metastases. A phase II trial was done in patients with advanced melanoma. Indomethacin and ranitidine were begun at least one week before IL-2. Of the objective responses in 3 patients, 2 were achieved on ranitidine and indomethacin alone, before start of IL-2. Indomethacin and ranitidine may be responsible for some responses in melanoma patients previously attributed to IL-2.